Drosophila PDZ-GEF a novel component of the MAP kinase signaling pathway

Abstract

PDZ-GEF is a novel family of guanine nucleotide exchange factor for Rap1. Here I isolated Drosophila PDZ-GEF (dPDZ-GEF) which contains the all the conserved domains of mammalian and nematode PDZ-GEF including cNMP-binding, Ras exchange motif, PDZ, RA, and GEF domains. dPDZ-GEF loss-of-function mutants were defective in the development of various organs including eye, wing and ovaries, and this phenotype is strikingly similar to the phenotype of rolled mutant, implying that dPDZ-GEF functions upstream of the MAPK pathway. Indeed, we found that dPDZ-GEF is specifically involved in photoreceptor cell differentiation, facilitating its neuronal fate via activation of the MAPK pathway. Rap1 was found to link dPDZ-GEF to the MAPK pathway; however, Ras was not involved in the regulation of the MAPK pathway by dPDZ-GEF, and actually had an inhibitory function. Collectively, our findings identify dPDZ-GEF as a novel upstream regulator of the MAPK signaling pathway, and demonstrate the presence of a novel, Ras-independent mechanism for activating the MAPK signaling pathway.